Erratum in

Nat Neurosci. 2010 Aug;13(8):1033

Abstract

We found that development of obesity was coupled with emergence of a progressively worsening deficit in neural reward responses. Similar changes in reward homeostasis induced by cocaine or heroin are considered to be crucial in triggering the transition from casual to compulsive drug-taking. Accordingly, we detected compulsive-like feeding behavior in obese but not lean rats, measured as palatable food consumption that was resistant to disruption by an aversive conditioned stimulus. Striatal dopamine D2 receptors (D2Rs) were downregulated in obese rats, as has been reported in humans addicted to drugs. Moreover, lentivirus-mediated knockdown of striatal D2Rs rapidly accelerated the development of addiction-like reward deficits and the onset of compulsive-like food seeking in rats with extended access to palatable high-fat food. These data demonstrate that overconsumption of palatable food triggers addiction-like neuroadaptive responses in brain reward circuits and drives the development of compulsive eating. Common hedonic mechanisms may therefore underlie obesity and drug addiction.

Figures

Figure 1. Weight gain and reward dysfunction…

Figure 1. Weight gain and reward dysfunction in rats with extended access to a cafeteria…

Figure 1. Weight gain and reward dysfunction in rats with extended access to a cafeteria diet

(a) Chow-only, restricted access and extended access rats were sub-divided into two groups per access condition based on a median split of body weights; light (L) or heavy (H). (b) The entire striatal complex was collected from all rats and D2R levels in each group measured by Western blotting. The membrane-associated post-synaptic D2R band was resolved at 70 kDa, and the protein-loading control is displayed below (β-actin, 43 kDa). Full-length immunoblots are displayed in Supplementary Figure 12. (c) Relative amounts of D2R in the striatum of chow-only, restricted and extended access rats were quantified by densitometry (F2,6=5.2, P < 0.05, main effect of Access; *P < 0.05 compared with Chow-only-L group).

Figure 5. Lentivirus-mediated knockdown of striatal D2R…

Figure 5. Lentivirus-mediated knockdown of striatal D2R expression

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( a ) Graphical representation of the…

Figure 5. Lentivirus-mediated knockdown of striatal D2R expression

(a) Graphical representation of the striatal areas in which Lenti-D2Rsh was overexpressed. Green circles in the left striatal hemisphere represent the locations at which viral infusions were targeted. Green staining in the right striatal hemisphere is a representative immunochemistry staining for GFP from the brain of a Lenti-D2Rsh rat. (b) Representative immunoblot of the decreased D2R expression in the striatum of Lenti-D2Rsh rats. Full-length immunoblots are displayed in Supplementary Figure 13. (c) Relative amounts of D2R in the striatum of Lenti-Control and Lenti-D2Rsh rats were quantified by densitometry (*P < 0.05 compared with the Lenti-Control group, post-hoc test). (d) Infection of glial cells in the striatum by the Lenti-D2Rsh vector was not detected. Green staining is GFP from virus; red is the astrocyte marker glial fibrillary acidic protein [GFAP]; cell nuclei are highlighted by DAPI staining in blue. The white arrows indicate a highly localized area of gliosis found only at the site of virus injection in the striatum and not in the surrounding tissues into which the virus has diffused. Even in this area none of the astrocytes were GFP-positive. The yellow arrows in the magnified image highlight the typical GFP-negative astrocytes that were detected. (e) High levels of neuronal infection in the striatum by the Lenti-D2Rsh vector were detected. Green staining is GFP from virus; red is the neuronal nuclear marker NeuN; cell nuclei are highlighted by DAPI staining in blue. The yellow arrows in the magnified image highlight GFP-positive and NeuN-positive neurons in the striatum. (f) A higher magnification image of a virally infected (GFP-positive) neuron in the striatum of Lenti-D2Rsh rats that displays the typical morphological features of medium spiny neurons.